Benjamin Lo

Subarachnoid Hemorrhage International Trialists Data Repository (SAHIT)

The outcome of patients with aneurysmal subarachnoid hemorrhage (SAH) has improved slowly over the past 25 years. This improvement may be due to early aneurysm repair by endovascular or open means, use of nimodipine, and better critical care management. Despite this improvement, mortality remains at about 40%, and many survivors have permanent neurologic, cognitive, and neuropsychologic deficits. Randomized clinical trials have tested pharmacologic therapies, but few have been successful. There are numerous explanations for the failure of these trials, including ineffective interventions, inadequate sample size, treatment side effects, and insensitive or inappropriate outcome measures. Outcome often is evaluated on a good-bad dichotomous scale that was developed for traumatic brain injury 40 years ago. To address these issues, we established the Subarachnoid Hemorrhage International Trialists (SAHIT) data repository. The primary aim of the SAHIT data repository is to provide a unique resource for prognostic analysis and for studies aimed at optimizing the design and analysis of phase III trials in aneurysmal SAH. With this aim in mind, we convened a multinational investigator meeting to explore merging individual patient data from multiple clinical trials and observational databases of patients with SAH and to create an agreement under which such a group of investigators could submit data and collaborate. We welcome collaboration with other investigators.

Prognostic value of premorbid hypertension and neurological status in aneurysmal subarachnoid hemorrhage: pooled analyses of individual patient data in the SAHIT repository.

OBJECT The literature has conflicting reports about the prognostic value of premorbid hypertension and neurological status in aneurysmal subarachnoid hemorrhage (SAH). The aim of this study was to investigate the prognostic value of premorbid hypertension and neurological status in the SAH International Trialists repository. METHODS Patient-level meta-analyses were conducted to investigate univariate associations between premorbid hypertension (6 studies; n = 7249), admission neurological status measured on the World Federation of Neurosurgical Societies (WFNS) scale (10 studies; n = 10,869), and 3-month Glasgow Outcome Scale (GOS) score. Multivariable analyses were performed to sequentially adjust for the effects of age, CT clot burden, aneurysm location, aneurysm size, and modality of aneurysm repair. Prognostic associations were estimated across the ordered categories of the GOS using proportional odds models. Nagelkerkes R(2) statistic was used to quantify the added prognostic value of hypertension and neurological status beyond those of the adjustment factors. RESULTS Premorbid hypertension was independently associated with poor outcome, with an unadjusted pooled odds ratio (OR) of 1.73 (95% confidence interval [CI] 1.50-2.00) and an adjusted OR of 1.38 (95% CI 1.25-1.53). Patients with a premorbid history of hypertension had higher rates of cardiovascular and renal comorbidities, poorer neurological status (p ≤ 0.001), and higher odds of neurological complications including cerebral infarctions, hydrocephalus, rebleeding, and delayed ischemic neurological deficits. Worsening neurological status was strongly independently associated with poor outcome, including WFNS Grades II (OR 1.85, 95% CI 1.68-2.03), III (OR 3.85, 95% CI 3.32-4.47), IV (OR 5.58, 95% CI 4.91-6.35), and V (OR 14.18, 95% CI 12.20-16.49). Neurological status had substantial added predictive value greater than the combined value of other prognostic factors (R(2) increase > 10%), while the added predictive value of hypertension was marginal (R(2) increase < 0.5%). CONCLUSIONS This study confirmed the strong prognostic effect of neurological status as measured on the WFNS scale and the independent but weak prognostic effect of premorbid hypertension. The effect of premorbid hypertension could involve multifactorial mechanisms, including an increase in the severity of initial bleeding, the rate of comorbid events, and neurological complications.

Effect of intrathecal milrinone injection via lumbar catheter on delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

OBJECTIVE Delayed cerebral ischemia (DCI) is an important complication after aneurysmal subarachnoid hemorrhage (aSAH). Although intrathecal milrinone injection via lumbar catheter to prevent DCI has been previously reported to be safe and feasible, its effectiveness remains unknown. The goal of this study was to evaluate whether intrathecal milrinone injection treatment after aSAH significantly reduced the incidence of DCI. METHODS The prospectively maintained aSAH database was used to identify patients treated between January 2010 and December 2015. The cohort included 274 patients, with group assignment based on treatment with intrathecal milrinone injection or not. A propensity score model was generated for each patient group, incorporating relevant patient variables. RESULTS After propensity score matching, 99 patients treated with intrathecal milrinone injection and 99 without treatment were matched on the basis of similarities in their demographic and clinical characteristics. There were significantly fewer DCI events (4% vs 14%, p = 0.024) in patients treated with intrathecal milrinone injection compared with those treated without it. However, there were no significant differences between the 2 groups with respect to their 90-day functional outcomes (46% vs 36%, p = 0.31). The likelihood of chronic secondary hydrocephalus, meningitis, and congestive heart failure as complications of intrathecal milrinone injection therapy was also similar between the groups. CONCLUSIONS In propensity score-matched groups, the intrathecal administration of milrinone via lumbar catheter showed significant reduction of DCI following aSAH, without an associated increase in complications.

Health-Related Quality of Life After Aneurysmal Subarachnoid Hemorrhage: New Data from a Large Series in Germany

I n this issue of WORLD NEUROSURGERY, Tjahjadi et al. from Germany assessed health-related quality of life (HRQoL) in 253 patients who survived aneurysmal subarachnoid hemorrhage (SAH). Data were collected from patients, a relative, caregiver, or person in regular contact with the patient. The time after the SAH when data were collected was unclear but seems to have been between 1 and 10 years. The data were the short form 36, short form 12, a nonstandardized survey, and visual analogue scales (we are not sure what was on the visual analogue scales; the results describe 4 scales judging patient state of health and its influence on daily activities and work). The authors present a great deal of data, but the summary is that about half of the patients experienced chronic reductions in various aspects of HRQoL. Poor HRQoL was more likely in poor-grade patients, those with longer hospital stay, higher Fisher score, delirium, hydrocephalus, and seizures. Multivariate analysis is mentioned in the statistical methods, but we could not tell if those factors were found in univariate or multivariate analysis.

Reflux of Anterior Spinal Artery Predicts Recurrent Posterior Circulation Stroke in Bilateral Vertebral Artery Disease

Backgrounds and Purpose— Predictive value of reflux of anterior spinal artery for recurrent posterior circulation ischemia in bilateral vertebral arteries steno-occlusive disease was evaluated. Methods— We retrospectively reviewed 55 patients with symptomatic posterior circulation stroke caused by bilateral stenotic (>70%) lesions of the vertebral artery. We investigated any correlation of clinical and angiographic characteristics including collateral flow patterns, with recurrent stroke. Risk factors for poor 3-month functional outcome were also evaluated. Results— Recurrent posterior circulation stroke was observed in 15 (27.3%) patients. Multivariable analysis using Cox proportional hazards model showed anterior spinal artery reflux as a significant risk factor for stroke recurrence (adjusted hazard ratio, 19.3 [95% confidence interval, 5.35–69.9]; P<0.001). Anterior spinal artery reflux was also correlated with poor functional outcome (modified Rankin Scale score, 3–6; adjusted odds ratio, 7.41 [95% confidence interval, 1.24–44.4]; P=0.028). Conclusions— In patients with symptomatic bilateral vertebral artery occlusive disease, anterior spinal artery reflux predicted recurrent posterior circulation stroke and poor functional outcome.

The SAFARI Score to Assess the Risk of Convulsive Seizure During Admission for Aneurysmal Subarachnoid Hemorrhage

BACKGROUND Seizure is a significant complication in patients under acute admission for aneurysmal SAH and could result in poor outcomes. Treatment strategies to optimize management will benefit from methods to better identify at‐risk patients. OBJECTIVE To develop and validate a risk score for convulsive seizure during acute admission for SAH. METHODS A risk score was developed in 1500 patients from a single tertiary hospital and externally validated in 852 patients. Candidate predictors were identified by systematic review of the literature and were included in a backward stepwise logistic regression model with in‐hospital seizure as a dependent variable. The risk score was assessed for discrimination using the area under the receiver operator characteristics curve (AUC) and for calibration using a goodness‐of‐fit test. RESULTS The SAFARI score, based on 4 items (age ≥ 60 yr, seizure occurrence before hospitalization, ruptured aneurysm in the anterior circulation, and hydrocephalus requiring cerebrospinal fluid diversion) had AUC = 0.77, 95% confidence interval (CI): 0.73‐0.82 in the development cohort. The validation cohort had AUC = 0.65, 95% CI 0.56‐0.73. A calibrated increase in the risk of seizure was noted with increasing SAFARI score points. CONCLUSION The SAFARI score is a simple tool that adequately stratified SAH patients according to their risk for seizure using a few readily derived predictor items. It may contribute to a more individualized management of seizure following SAH.